Clefting of the lip and palate (CLP) is one of the most common craniofacial anomalies, with a rate of 1:650 in the United States population. Over 250 genetically based syndromes exist which include cleft lip or palate as a feature of their clinical presentation. In FY 1994, the NIDR initiated a collaborative research study with the Lancaster Cleft Palate Clinic in Lancaster, Pa. The Lancaster Collaborative Study of Cleft Lip and Palate (LCS) is a large scale epidemiologic study, involving the comprehensive mapping of highly informative DNA markers, utilizing the clinical population from the Lancaster Cleft Palate Clinic and affiliated clinics. Semiautomatic gene mapping technologies developed by MEDIB in ongoing CLP studies will be applied to map gene/genes responsible for clefting. The study population will consist of approximately 2300 patients and controls including 225 families with more than one child affected with CLP. DNA extracted from blood or buccal cells will be genotyped utilizing 29 panels of 12-17 microsatellite loci and genetic linkage and association analyses will be performed.